Integrated metabolomics and transcriptomics reveal glyphosate based‐herbicide induced reproductive toxicity through disturbing energy and nucleotide metabolism in mice testes

Glyphosate is a widely used herbicide that has deleterious effects on animal reproduction. However, details regarding the systematic mechanisms of glyphosate-induced reproductive toxicity are limited. This study aimed to investigate the toxic effects of glyphosate-based herbicide (GBH) on reproduction in mice exposed to 0 (control group), 50 (low-dose group), 250 (middle-dose group), and 500 (high-dose group) mg/kg/day GBH for 30 days. Toxicological parameters, metabolomics, and transcriptomics were performed to reveal GBH-induced reproductive toxicity. Our findings demonstrated that GBH exposure damaged mitochondrial pyknosis and the nuclear membrane of spermatogonia. GBH triggered a significant increase in sperm malformations in the high-dose group. Omics data showed that GBH impaired the Krebs cycle and respiratory chain, blocked pyruvate metabolism and glycolysis/gluconeogenesis, and influenced the pentose phosphate pathway and nucleotide synthesis and metabolism. Overall, the multi-omics results revealed systematic and comprehensive evidence of the adverse effects of GBH exposure, providing new insights into the reproductive toxicity of organophosphorus pesticides.